The long term research goals of this project are to understand the mechanisms involved in fibroblast growth factor (FGF) regulation of cellular proliferation and differentiation. The overall aims of this project are to delineate the mechanisms by which FGF mediates the repression of skeletal muscle differentiation and stimulation of myoblast proliferation. The specific aims are purification and characterization of fibroblast growth factor receptor(s) (FGFR), production of monoclonal and polyclonal antibodies to FGFR and isolation of FGFR cDNA clones for structure- function studies of FGFR, analysis of FGFR synthesis, metabolism, and regulation during skeletal muscle differentiation in vitro, and for localization, distribution, and analysis of FGFR regulation during embryonic development. Particular attention will be focused on the role of FGFR in the skeletal muscle cell lineage. Methodology pertinent to this project includes protein purification and sequencing, monoclonal and polyclonal antibody production, cDNA cloning, sequencing, and mutagenesis, cell transfection and stable expression of cDNA's. An analysis of FGFR, and its regulation may have major ramifications for understanding FGF's roles in normal and neoplastic cellular growth, and normal and tumor-induced angiogenesis. Furthermore, analysis of FGFR-mediated skeletal muscle growth and differentiation may have a direct impact on the treatment of degenerative neuromuscular diseases (particularly the muscular dystrophies) and on the treatment of muscle tumors (rhabdomyosarcomas).